We have been developing general procedures to create synthetic nano materials, that function as antibody and enzymes, from inexpensive and stable acrylic monomers.

1, Development of Plastic AntibodiesGeneral procedures for the creation of synthetic nanoparticles with biomacromolecular recognition sites are of significant interest as a route to stable, robust, and mass-produced substitutes for antibodies. Ideally, recognition of complex biological targets, including proteins, peptides, and carbohydrates, requires multiple functional groups that contact target molecules by a combination of electrostatic, hydrogen-bonding, van der Waals, and/or hydrophobic interactions. We have shown that copolymerization of optimized combination and ratio of functional acrylic-monomers creates synthetic polymer materials with molecular recognition sites for peptides and proteins. In addition to optimizing functional complementarity, the affinity sites can be further enhanced by molecular imprinting and/or affinity purification process. Those particles are capable of recognizing, neutralizing, and clearing toxic peptide and proteins even in the bloodstream of living animals. However, in contrast to antibodies whose exact sequence can be determined and cloned, polymerized materials result in heterogeneous structures with a distribution of recognition sites. Our goal is to achieve general strategy to create plastic antibodies with uniform molecular structure as "monoclonal plastic antibodies".

2, Development of Plastic EnzymesLife is a dissipate structure appears in the non-equilibrium open system. To maintain the structure, enzymes mediates most reactions in the body including molecular transportation, energy conversion and molecular conversion that are necessarily for the life. To keep the life alive, it is important for the each enzyme to recognize and bind to specific molecules and ions and catalyze specific reaction just in time. It is also very important to control binding and dissociating kinetics to keep the dissipate structure.One of the challenges for us is to construct synthetic molecular system like living life. So far, we found that target binding and dissociation kinetics of nanoparticles can be tuned by conformation change and polymer density of the particles. Binding constant to target proteins and ions can be reversibly switched on/off by temperature-induced phase transition of the polymer chains. By applying the fundamental findings, we are trying to develop inexpensive and scalable chemical process for the conversion of low temperature waste heat in to reusable chemical potential.

Y. Hoshino, T. Miyoshi, T. Jibiki, Y. Miura, Tuning pKa of Brønsted Acids in Stimuli Responsive Nanogel Particles by Proton- and Ion-Imprinting Strategy for Reversible Capture of Target Molecules, Affinity 2017, 2017.06, Synthetic materials that alter their binding affinity to target molecules in response to external stimuli have gained considerable attention as substitutes for protein based ligands. Recently, we revealed that pNIPAm-based NPs that show large and reversible pKa shifts can be prepared by the “proton imprinting” and “microenvironment imprinting” strategy. The pKa variation range of carboxylic acids in the NPs can further be tuned by designing structure of monomers containing Brønsted acids and tuning cross-linking density and size of NPs. The pKa variation range can be lowered/raised to be 4-9 by stabilizing/destabilizing carboxylate anions by modifying the acids with electron withdrawing/donating group. The pKa of acids can also be lowered dramatically by imprinting cationic functional group such as guanidium group around the carboxylate anions.Our results provide a guide for designing stable and inexpensive materials for many biological and chemical applications as temperature-dependent affinity media and pH modifiers..